Histone lysine methylation is an important modification that is associated with chromatin remodeling and gene regulation and has been implicated in drug-induced neuronal plasticity mechanisms, memory formation and cognition (Gupta et al., 2010; Maze et al., 2010, 2011; Schaefer et al., 2009; Shinkai & Tachibana, 2011). Tri-methylation of H3K4 (H3K4me3) is associated with active chromatin and is potentiated by acetylation of H3K9 and 14, providing further evidence of cross-talk between histone modifications and transcriptional regulation (Vermeulen et al., 2007). In a model of contextual fear conditioning, H3K4me3 was shown to be increased in the promoters of BDNF and Zif-268 genes within the CA1 region of the hippocampus. Moreover, infusion of an HDAC inhibitor directly into CA1 caused an increase in the transcriptionally active H3K4me3 and a simultaneous decrease in the transcriptionally repressive H3K9me2 (Gupta et al., 2010). In an invertebrate model of Huntington Disease, lower levels of the H3K4 de-methylase SMCX/Jarid1c have been shown to be neuroprotective, a mechanism that is also conserved in a mouse model (Vashishtha et al., 2013). Contrary to H3K4, methylation at H3K9 is a repressive
